Antibacterial aminoglycoside analogs
View Patent ↗Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Q 1 and Q 2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
1. A compound having the following structure (I):
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein:
Q 1 is —NHR 1 ;
Q 2 is
R 1 is C 2 -C 6 alkyl substituted with at least one hydroxyl;
R 2 is hydrogen or C 1 -C 6 alkyl optionally substituted with one or more halogen, hydroxyl or amino; and
n is an integer from 1 to 4.
2. A compound of claim 1 wherein R 1 is C 2 -C 6 alkyl substituted with one hydroxyl.
3. A compound of claim 2 wherein R 1 is —(CH 2 ) m OH, wherein m is an integer from 2 to 6.
4. A compound of claim 3 wherein R 1 is —(CH 2 ) 2 OH or —(CH 2 ) 3 OH.
5. A compound of claim 4 wherein R 1 is —(CH 2 ) 2 OH.
6. A compound of claim 2 wherein R 1 is —(CH 2 ) p CH(CH 3 )OH, wherein p is an integer from 1 to 4.
7. A compound of claim 6 wherein R 1 is —CH 2 CH(CH 3 )OH or —(CH 2 ) 2 CH(CH 3 )OH.
8. A compound of claim 1 wherein R 1 is C 2 -C 6 alkyl substituted with two hydroxyl groups.
9. A compound of claim 8 wherein R 1 is —CH 2 CH(OH)(CH 2 ) q OH wherein q is an integer from 1 to 4.
10. A compound of claim 9 wherein R 1 is —CH 2 CH(OH)CH 2 OH or —CH 2 CH(OH)(CH 2 ) 2 OH.
11. A compound of claim 8 wherein R 1 is —(CH 2 ) r CH(CH 2 OH) 2 wherein r is 0 or an integer from 1 to 3.
12. A compound of claim 11 wherein R 1 is —CH 2 CH(CH 2 OH) 2 or —CH(CH 2 OH) 2 .
13. A compound of claim 1 wherein R 2 is hydrogen.
14. A compound of claim 13 wherein Q 2 is:
15. A compound of claim 14 wherein Q 2 is:
16. A compound of claim 14 wherein Q 2 is:
17. A compound of claim 1 having the configuration:
18. A compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
19. A compound of claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
20. A compound of claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition comprising a compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
22. A method of treating a bacterial infection in a mammal comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 .
23. A method of claim 22 wherein the bacterial infection is caused by an Acinetobacter baumannii bacterium.
24. A method of claim 22 wherein the bacterial infection is caused by a Pseudomonas aeruginosa bacterium.
25. A method of treating a bacterial infection in a mammal comprising administering to a mammal in need thereof an effective amount of a pharmaceutical composition of claim 21 .
26. A method of claim 25 wherein the bacterial infection is caused by an Acinetobacter baumannii bacterium.
27. A method of claim 25 wherein the bacterial infection is caused by a Pseudomonas aeruginosa bacterium.